Animals and their organs become patterned as they grow. One of the most intriguing and challenging questions in developmental biology today is how patterning and growth are coordinated in time and space. Dpp, a member of TGF-β superfamily, with its ability to regulate both processes, serves as a paradigm to answer this question. Our first aim focuses on the logic of transcriptional regulation by Smad proteins, the nuclear effectors of the TGF-β pathways. The Drosophila Smad proteins, Mad and Medea, lead to activation of some target genes while inhibiting others. The putative cofactors required for Dpp-dependent activation have not been identified thus far. Here, I will test the hypothesis that T-box containing proteins, Dorsocross 1, 2, and 3, fulfill this function. In the second part, I aim to monitor Dpp signaling dynamics in vivo. I will fuse Dpp responsive elements to cDNA constructs that encode highly unstable versions of GFP or RFP allowing us to detect small and transient fluctuations in Dpp response. These experiments aim to achieve a detailed spatio-temporal analysis of the dynamics of Dpp signaling in growing tissues. Such in vivo studies will allow putting forward or excluding certain models of how Dpp exerts its multiple functions.
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